BXCL501 · program

Dexmedetomidine sublingual film (BXCL501) for Schizophrenia

Filed (NDA)ActiveBioXcel Therapeutics, Inc. (BTAI)
  • Fast Track

Indications for BXCL501: Acute Stress Disorder · Phase 2 Schizophrenia · Filed (NDA) Opioid use disorder · Phase 1/2 Agitation in Alzheimer's disease · Phase 3

Supplemental NDA (sNDA) FILED to expand the IGALMI (BXCL501, sublingual dexmedetomidine) label to AT-HOME / outpatient use for the acute treatment of agitation associated with bipolar I/II disorder or schizophrenia. IGALMI is already FDA-approved (Apr 2022) for this agitation indication but only in a healthcare-supervised setting; the SERENITY At-Home program seeks the first approved at-home (patient/caregiver-administered) agitation therapy. The pivotal study is SERENITY III / 'SERENITY At-Home' (NCT05658510, Phase 3, 2-part, 452 enrolled). Part 1 (single-day in-clinic, 60 mcg, PEC change at 2h) MISSED its primary efficacy endpoint at 2h (p=0.077; 4h p=0.049; PEC-responder secondary p=0.019) when reported 25 May 2023. Part 2 (12-week at-home, 120 mcg PRN) was a SAFETY trial whose primary tolerability endpoint was MET (27 Aug 2025), with positive but non-powered exploratory efficacy (mCGI-S reduction at 2h across 2,433 episodes, p<0.05). Following a positive pre-sNDA meeting (18 Aug 2025), BioXcel submitted the sNDA on 14 Jan 2026; the FDA accepted it with a PDUFA target action date of 14 Nov 2026 (announced 01 Apr 2026). BXCL501 holds Fast Track designation for this indication. Reviewer caveat: BioXcel disclosed substantial-doubt going-concern as of Q1 2026.

Data current as of

Development timeline

Filed (NDA)Jan 2026 – Nov 2026
  1. UpcomingFDA decision (PDUFA) on the sNDA to expand IGALMI (BXCL501) to at-home use for acute agitation in bipolar disorders or schizophrenia expected 14 Nov 2026.↗
  2. FDA ACCEPTED the sNDA for IGALMI at-home use; PDUFA target action date set for 14 Nov 2026. If approved, would be the first FDA-approved at-home acute treatment for agitation associated with bipolar disorders or schizophrenia.↗
  3. BioXcel SUBMITTED the sNDA to the FDA for IGALMI label expansion to at-home use for acute agitation associated with bipolar disorders or schizophrenia, supported by the SERENITY At-Home (Part 2) safety trial.↗
Phase 3May 2023 – Aug 2025
  1. metSERENITY At-Home (NCT05658510 Part 2) Phase 3 safety trial MET its primary endpoint: at-home 120 mcg sublingual dexmedetomidine well tolerated across 2,437 agitation episodes, supporting the sNDA.↗
  2. Positive FDA pre-sNDA meeting: FDA aligned with BioXcel that the planned sNDA regulatory package (content, format, clinical/nonclinical data, CMC) is sufficient to support submission for at-home use of IGALMI in bipolar/schizophrenia agitation.↗
  3. SERENITY III (NCT05658510) Part 1 topline: the single-day in-clinic in-clinic 60 mcg arm did NOT meet the primary efficacy endpoint (change in PEC vs placebo at 2h, p=0.077); the 4h timepoint was nominally significant (p=0.049) and the PEC-responder secondary at 2h was significant (52% responders, p=0.019). 60 mcg well tolerated, no SAEs.↗

Readouts

  • PDUFA 14 Nov 2026AnticipatedRegulatory

    FDA decision (PDUFA) on the sNDA to expand IGALMI (BXCL501) to at-home use for acute agitation in bipolar disorders or schizophrenia expected 14 Nov 2026. ↗

  • 2025-08-27ReportedTopline datametNCT05658510

    SERENITY At-Home (NCT05658510 Part 2) Phase 3 safety trial MET its primary endpoint: at-home 120 mcg sublingual dexmedetomidine well tolerated across 2,437 agitation episodes, supporting the sNDA. ↗

Clinical trials in Schizophrenia

NCT05658510SERENITY III / SERENITY At-HomePhase 3Completedn=452

Efficacy And Safety of BXCL501 Evaluated For At-Home Use In A Multisite Double-Blind Placebo-Controlled Trial For Agitation Associated With Schizophrenia And Bipolar Disorder (SERENITY III)

Started Nov 2022· Primary completion Aug 2025· 📍 24 sites across 1 country (United States)

missedprimaryPart 1 (in-clinic): change from baseline in PEC total score at 2 hours, 60 mcg vs placebo (0.077)

Part 1 single-day in-clinic primary efficacy endpoint NOT met: change in PEC at 2h with 60 mcg did not reach statistical significance vs placebo (p=0.077). The 4h timepoint was nominally significant (p=0.049) and the PEC-responder secondary at 2h was significant (52% responders, p=0.019). 60 mcg = half the lowest approved IGALMI dose; well tolerated, no SAEs.

metprimaryPart 2 (at-home): incidence of serious and treatment-emergent adverse events through 12 weeks (120 mcg PRN)

Part 2 at-home pivotal SAFETY primary endpoint MET: 120 mcg sublingual dexmedetomidine was well tolerated as-needed at home across 2,437 agitation episodes treated in 208 patients over 12 weeks, with a safety profile consistent with the approved IGALMI label. 246 patients randomized (45% bipolar I/II, 55% schizophrenia).

metsecondaryPart 2 (at-home): exploratory mean change from baseline in modified CGI-S at 2 hours vs placebo (120 mcg) (<0.05)

Exploratory (non-powered) efficacy: BXCL501 produced a significant mean reduction in mCGI-S at 2h vs placebo across 2,433 treated episodes (p<0.05), with benefit sustained on repeated dosing and largest effect in episodes rated severe at baseline (ASCP 2026 analysis). The trial was not powered for efficacy.

Formulations

FormulationRouteRegimenPharmacokinetics
Dexmedetomidine sublingual film (IGALMI)oral dissolving film
120 mcg and 180 mcg films (cuttable to 60 mcg / 90 mcg); initial dose with up to two additional doses at least 2 hours apart
SublingualSingle doset½ 2.8 h · Tmax 2 h · F 72%

Mechanism of action (compound-wide)

Dexmedetomidine is a potent, highly selective alpha-2 adrenergic receptor agonist (the pharmacologically active S-enantiomer of medetomidine), with reported alpha-2:alpha-1 selectivity on the order of ~1600:1. Agonism at the presynaptic alpha-2A adrenoceptor (ADRA2A) in the locus coeruleus reduces noradrenergic outflow, producing sedation/anxiolysis without significant respiratory depression. In agitation, sublingual dexmedetomidine is hypothesized to calm hyperadrenergic arousal that drives acute agitation episodes. Alpha-2B and alpha-2C subtypes are additional adrenoceptor targets.

TargetActionAffinity
alpha-2A adrenoceptorprimaryADRA2AAgonist—ⓘ
alpha-2B adrenoceptorADRA2BAgonist—ⓘ
alpha-2C adrenoceptorADRA2CAgonist—ⓘ

← Full BXCL501 compound page (identity, identifiers, all indications)

Sources

  1. alpha-2A adrenoceptor (ADRA2A, object 25) — dexmedetomidine listed as partial agonist — IUPHAR/BPS Guide to Pharmacology
  2. BioXcel announces FDA acceptance of sNDA for at-home use of IGALMI; PDUFA target action date 14 Nov 2026 — BioXcel Therapeutics (GlobeNewswire wire release)
  3. BioXcel announces positive FDA pre-sNDA meeting comments for BXCL501 sNDA in agitation associated with bipolar disorders or schizophrenia — BioXcel Therapeutics (GlobeNewswire wire release)
  4. BioXcel announces SERENITY At-Home pivotal Phase 3 safety trial met its primary endpoint in support of sNDA for IGALMI label expansion — BioXcel Therapeutics (GlobeNewswire wire release)
  5. BioXcel announces topline results from Part 1 of pivotal SERENITY III trial of BXCL501 for at-home use (in-clinic 60 mcg; PEC at 2h missed, p=0.077) — BioXcel Therapeutics / IR
  6. BioXcel presents new SERENITY At-Home exploratory efficacy data (mCGI-S across severity, 2,433 episodes) at the 2026 ASCP Annual Meeting — BioXcel Therapeutics (GlobeNewswire wire release)
  7. BioXcel submits sNDA to FDA for IGALMI label expansion in the at-home setting (submitted 14 Jan 2026) — BioXcel Therapeutics (GlobeNewswire wire release)
  8. Dexmedetomidine (ligand 521) — selective alpha-2 adrenoceptor agonist — IUPHAR/BPS Guide to Pharmacology
  9. IGALMI (dexmedetomidine film) - FDA prescribing information — DailyMed / NIH
  10. SERENITY III / SERENITY At-Home — Phase 3, 2-part (in-clinic 60 mcg + at-home 120 mcg) BXCL501 in agitation associated with schizophrenia and bipolar disorder (NCT05658510) — ClinicalTrials.gov